The polymerase chain reaction, or PCR, provides a highly efficient method of isolating a desired gene sequence(s) from different DNA samples. One general requirement is that sequence information is available from both ends of the fragment to be amplified in order to synthesize specific amplification primers. The expense of sequencing DNA and then chemically synthesizing primers still limits the scope of many applications. In many investigations it would therefore be most helpful if the steps of DNA sequencing and oligonucleotide synthesis could be avoided entirely before genomic fragments are amplified by PCR. This is true for instance for the large programs designed to analyze the degree of polymorphism of specific DNA segments in individuals in a population, in order to identify polymorphic markers in the human or other genomes. Such genetic markers are required for mapping genetic disease and to establish or extend genetic linkage maps for a variety of organisms.
One approach which partially overcomes the above problem is the use of relatively nonspecific amplification with a limited set of primers under nonstringent conditions, so called RAPD markers. These markers serve as a means to establish relatively random polymorphic markers, analyzable by PCR without requiring DNA sequencing and chemical oligonucleotide synthesis of specific primers.